rs1914663

Positions:

• chr10-79612197-C-T

Variant summary

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

The NM_005411.5(SFTPA1):​c.173-115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0923 in 1,605,492 control chromosomes in the GnomAD database, including 7,613 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 0.11 (1081 hom., cov: 32)
  • Exomes 𝑓: 0.090 (6532 hom.)
• Consequence: SFTPA1 NM_005411.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

Genes affected

SFTPA1 (HGNC:10798): (surfactant protein A1) This gene encodes a lung surfactant protein that is a member of a subfamily of C-type lectins called collectins. The encoded protein binds specific carbohydrate moieties found on lipids and on the surface of microorganisms. This protein plays an essential role in surfactant homeostasis and in the defense against respiratory pathogens. Mutations in this gene are associated with idiopathic pulmonary fibrosis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPA1	NM_005411.5	c.173-115C>T		intron_variant		ENST00000398636.8	NP_005402.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPA1	ENST00000398636.8	c.173-115C>T		intron_variant		1	NM_005411.5	ENSP00000381633.3
SFTPA1	ENST00000419470.6	c.218-115C>T		intron_variant		1		ENSP00000397082.2
SFTPA1	ENST00000428376.6	c.173-115C>T		intron_variant		1		ENSP00000411102.2
SFTPA1	ENST00000429958.5	c.173-115C>T		intron_variant		1		ENSP00000395527.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16923 AN: 152004 Hom.: 1081 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.0736

Gnomad FIN AF: 0.0985

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0877

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.0903 AC: 131242 AN: 1453370 Hom.: 6532 AF XY: 0.0895 AC XY: 64726 AN XY: 723188

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.0949

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.0646

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.0828

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.111 AC: 16951 AN: 152122 Hom.: 1081 Cov.: 32 AF XY: 0.113 AC XY: 8410 AN XY: 74350

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.0738

Gnomad4 FIN AF: 0.0985

Gnomad4 NFE AF: 0.0877

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0981 Hom.: 88

Bravo AF: 0.115

Asia WGS AF: 0.162 AC: 562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.13
DANN	Benign	0.53

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: rs1914663; hg19: chr10-81371953; COSMIC: COSV64867546; COSMIC: COSV64867546;