NM_003019.5:c.550+187A>G

Variant names:

• chr10-79941767-T-C
• rs911887
• NM_003019.5:c.550+187A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003019.5(SFTPD):​c.550+187A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,908 control chromosomes in the GnomAD database, including 12,532 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.40 (12532 hom., cov: 31)
• Consequence: SFTPD NM_003019.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.08
• Publications: 23 publications found

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]

ENSG00000283913 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 10-79941767-T-C is Benign according to our data. Variant chr10-79941767-T-C is described in ClinVar as [Benign]. Clinvar id is 1263839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPD	NM_003019.5	c.550+187A>G		intron_variant	Intron 5 of 7	ENST00000372292.8	NP_003010.4
SFTPD	XM_011540087.2	c.550+187A>G		intron_variant	Intron 5 of 7		XP_011538389.1
SFTPD	XM_011540088.3	c.433+187A>G		intron_variant	Intron 4 of 6		XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPD	ENST00000372292.8	c.550+187A>G		intron_variant	Intron 5 of 7	1	NM_003019.5	ENSP00000361366.3

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60906 AN: 151790 Hom.: 12531 Cov.: 31

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.371

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.401 AC: 60941 AN: 151908 Hom.: 12532 Cov.: 31 AF XY: 0.402 AC XY: 29853 AN XY: 74206

African (AFR) AF: 0.386 AC: 15990 AN: 41416

American (AMR) AF: 0.301 AC: 4594 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1019 AN: 3470

East Asian (EAS) AF: 0.370 AC: 1905 AN: 5142

South Asian (SAS) AF: 0.410 AC: 1972 AN: 4808

European-Finnish (FIN) AF: 0.512 AC: 5402 AN: 10560

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.423 AC: 28731 AN: 67924

Other (OTH) AF: 0.368 AC: 773 AN: 2100

Alfa AF: 0.410 Hom.: 48568

Bravo AF: 0.384

Asia WGS AF: 0.400 AC: 1396 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0070
DANN	Benign	0.35
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs911887; hg19: chr10-81701523;