dbSNP rs17885228: SFTPD:p.Lys99Lys (chr10-79942782-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003019.5(SFTPD):c.297G>A(p.Lys99Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,612,094 control chromosomes in the GnomAD database, including 454 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 136 hom., cov: 32)

Exomes 𝑓: 0.017 ( 318 hom. )

Consequence

SFTPD
NM_003019.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.138

Publications

5 publications found

Variant links:

Genes affected

SFTPD (HGNC:10803): (surfactant protein D) The protein encoded by this gene is part of the innate immune response, protecting the lungs against inhaled microorganisms and chemicals. The encoded protein may also be involved in surfactant metabolism. [provided by RefSeq, Jul 2015]

SFTPD links:

ENSG00000283913 (HGNC:):

ENSG00000283913 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 10-79942782-C-T is Benign according to our data. Variant chr10-79942782-C-T is described in ClinVar as Benign. ClinVar VariationId is 165217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.138 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPD	NM_003019.5 link	c.297G>A	p.Lys99Lys	synonymous_variant	Exon 3 of 8	ENST00000372292.8	NP_003010.4	P35247
SFTPD	XM_011540087.2 link	c.297G>A	p.Lys99Lys	synonymous_variant	Exon 3 of 8		XP_011538389.1	P35247
SFTPD	XM_011540088.3 link	c.297G>A	p.Lys99Lys	synonymous_variant	Exon 3 of 7		XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPD	ENST00000372292.8 link	c.297G>A	p.Lys99Lys	synonymous_variant	Exon 3 of 8	1	NM_003019.5	ENSP00000361366.3		P35247

Frequencies

GnomAD3 genomes

AF:

0.0329

AC:

5006

AN:

152140

Hom.:

133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0759

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0289

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0175

Gnomad OTH

AF:

0.0421

GnomAD2 exomes

AF:

0.0176

AC:

4436

AN:

251436

AF XY:

0.0171

show subpopulations

Gnomad AFR exome

AF:

0.0720

Gnomad AMR exome

AF:

0.0176

Gnomad ASJ exome

AF:

0.0195

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00245

Gnomad NFE exome

AF:

0.0180

Gnomad OTH exome

AF:

0.0217

GnomAD4 exome

AF:

0.0171

AC:

25025

AN:

1459836

Hom.:

318

Cov.:

AF XY:

0.0169

AC XY:

12264

AN XY:

726366

show subpopulations

African (AFR)

AF:

0.0767

AC:

2562

AN:

33422

American (AMR)

AF:

0.0179

AC:

801

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0193

AC:

503

AN:

26126

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00807

AC:

696

AN:

86212

European-Finnish (FIN)

AF:

0.00296

AC:

158

AN:

53420

Middle Eastern (MID)

AF:

0.0500

AC:

288

AN:

5760

European-Non Finnish (NFE)

AF:

0.0168

AC:

18636

AN:

1110148

Other (OTH)

AF:

0.0229

AC:

1380

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

1137

2274

3411

4548

5685

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

720

1440

2160

2880

3600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0330

AC:

5024

AN:

152258

Hom.:

136

Cov.:

AF XY:

0.0322

AC XY:

2399

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0762

AC:

3167

AN:

41556

American (AMR)

AF:

0.0289

AC:

442

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0190

AC:

AN:

3470

East Asian (EAS)

AF:

0.000388

AC:

AN:

5156

South Asian (SAS)

AF:

0.00601

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00226

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0175

AC:

1192

AN:

68018

Other (OTH)

AF:

0.0417

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

237

473

710

946

1183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0217

Hom.:

171

Bravo

AF:

0.0359

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0221

EpiControl

AF:

0.0251

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Lys99Lys in exon 3 of SFTPD: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 7.5% (331/4406) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs17885228). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

6.5

(source)

DANN

Benign

0.67

PhyloP100

0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over