rs726289

Positions:

• chr10-79947195-G-A
• chr10-79947195-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003019.5(SFTPD):​c.-3-533C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0789 in 152,316 control chromosomes in the GnomAD database, including 632 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.079 (632 hom., cov: 33)
• Consequence: SFTPD NM_003019.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPD	NM_003019.5	c.-3-533C>T		intron_variant		ENST00000372292.8	NP_003010.4
SFTPD	XM_011540087.2	c.-3-533C>T		intron_variant			XP_011538389.1
SFTPD	XM_011540088.3	c.-3-533C>T		intron_variant			XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPD	ENST00000372292.8	c.-3-533C>T		intron_variant		1	NM_003019.5	ENSP00000361366.3
SFTPD	ENST00000444384.3	c.37-533C>T		intron_variant		3		ENSP00000394325.1
ENSG00000283913	ENST00000421889.1	n.334-2833G>A		intron_variant		3
ENSG00000283913	ENST00000453174.7	n.962-2833G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0787 AC: 11978 AN: 152198 Hom.: 624 Cov.: 33

Gnomad AFR AF: 0.0633

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.0169

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.0484

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0678

Gnomad OTH AF: 0.0903

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

GnomAD4 genome AF: 0.0789 AC: 12012 AN: 152316 Hom.: 632 Cov.: 33 AF XY: 0.0816 AC XY: 6079 AN XY: 74478

Gnomad4 AFR AF: 0.0635

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.0778

Gnomad4 EAS AF: 0.0170

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.0484

Gnomad4 NFE AF: 0.0678

Gnomad4 OTH AF: 0.0941

Alfa AF: 0.0726 Hom.: 546

Bravo AF: 0.0858

Asia WGS AF: 0.128 AC: 445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs726289; hg19: chr10-81706951; COSMIC: COSV64852918;