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GeneBe

rs1051246

chr10-79938062-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_003019.5(SFTPD):c.918T>C(p.Ala306=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,613,872 control chromosomes in the GnomAD database, including 17,397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 2553 hom., cov: 32)
Exomes 𝑓: 0.13 ( 14844 hom. )

Consequence

SFTPD
NM_003019.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.53
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-79938062-A-G is Benign according to our data. Variant chr10-79938062-A-G is described in ClinVar as [Benign]. Clinvar id is 178808.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.53 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SFTPDNM_003019.5 linkuse as main transcriptc.918T>C p.Ala306= synonymous_variant 8/8 ENST00000372292.8
SFTPDXM_011540087.2 linkuse as main transcriptc.918T>C p.Ala306= synonymous_variant 8/8
SFTPDXM_011540088.3 linkuse as main transcriptc.801T>C p.Ala267= synonymous_variant 7/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SFTPDENST00000372292.8 linkuse as main transcriptc.918T>C p.Ala306= synonymous_variant 8/81 NM_003019.5 P1
SFTPDENST00000678361.1 linkuse as main transcriptn.3123T>C non_coding_transcript_exon_variant 4/4
SFTPDENST00000679234.1 linkuse as main transcriptn.3044T>C non_coding_transcript_exon_variant 5/5
ENST00000421889.1 linkuse as main transcriptn.234+1406A>G intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.166
AC:
25295
AN:
151994
Hom.:
2540
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.237
Gnomad AMI
AF:
0.0669
Gnomad AMR
AF:
0.272
Gnomad ASJ
AF:
0.254
Gnomad EAS
AF:
0.0172
Gnomad SAS
AF:
0.216
Gnomad FIN
AF:
0.0606
Gnomad MID
AF:
0.241
Gnomad NFE
AF:
0.120
Gnomad OTH
AF:
0.189
GnomAD3 exomes
AF:
0.157
AC:
39476
AN:
251466
Hom.:
4021
AF XY:
0.154
AC XY:
20874
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.239
Gnomad AMR exome
AF:
0.295
Gnomad ASJ exome
AF:
0.248
Gnomad EAS exome
AF:
0.0146
Gnomad SAS exome
AF:
0.202
Gnomad FIN exome
AF:
0.0703
Gnomad NFE exome
AF:
0.122
Gnomad OTH exome
AF:
0.177
GnomAD4 exome
AF:
0.134
AC:
195492
AN:
1461760
Hom.:
14844
Cov.:
33
AF XY:
0.135
AC XY:
98277
AN XY:
727154
show subpopulations
Gnomad4 AFR exome
AF:
0.242
Gnomad4 AMR exome
AF:
0.292
Gnomad4 ASJ exome
AF:
0.250
Gnomad4 EAS exome
AF:
0.0224
Gnomad4 SAS exome
AF:
0.202
Gnomad4 FIN exome
AF:
0.0709
Gnomad4 NFE exome
AF:
0.121
Gnomad4 OTH exome
AF:
0.155
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.167
AC:
25360
AN:
152112
Hom.:
2553
Cov.:
32
AF XY:
0.167
AC XY:
12395
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.237
Gnomad4 AMR
AF:
0.272
Gnomad4 ASJ
AF:
0.254
Gnomad4 EAS
AF:
0.0172
Gnomad4 SAS
AF:
0.216
Gnomad4 FIN
AF:
0.0606
Gnomad4 NFE
AF:
0.120
Gnomad4 OTH
AF:
0.194
Alfa
AF:
0.145
Hom.:
2549
Bravo
AF:
0.184
Asia WGS
AF:
0.172
AC:
597
AN:
3478
EpiCase
AF:
0.132
EpiControl
AF:
0.129

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineFeb 21, 2013Ala306Ala in exon 8 of SFTPD: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 22.9% (1010/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1051246). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
Cadd
Benign
0.27
Dann
Benign
0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1051246; hg19: chr10-81697818; COSMIC: COSV64852759; COSMIC: COSV64852759; API