rs1650223

Positions:

• chr10-79612228-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005411.5(SFTPA1):​c.173-84T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000402 in 1,610,404 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (0 hom.)
• Consequence: SFTPA1 NM_005411.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.55

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPA1	NM_005411.5	c.173-84T>C		intron_variant		ENST00000398636.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPA1	ENST00000398636.8	c.173-84T>C		intron_variant		1	NM_005411.5	P1
SFTPA1	ENST00000419470.6	c.218-84T>C		intron_variant		1
SFTPA1	ENST00000428376.6	c.173-84T>C		intron_variant		1		P1
SFTPA1	ENST00000429958.5	c.173-84T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.000375 AC: 57 AN: 152082 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.000956

GnomAD4 exome AF: 0.000405 AC: 591 AN: 1458206 Hom.: 0 AF XY: 0.000412 AC XY: 299 AN XY: 725510

Gnomad4 AFR exome AF: 0.000509

Gnomad4 AMR exome AF: 0.000336

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00111

Gnomad4 SAS exome AF: 0.000630

Gnomad4 FIN exome AF: 0.000281

Gnomad4 NFE exome AF: 0.000376

Gnomad4 OTH exome AF: 0.000432

GnomAD4 genome AF: 0.000375 AC: 57 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24 AN XY: 74410

Gnomad4 AFR AF: 0.000602

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000612 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.040
DANN	Benign	0.13

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: rs1650223; hg19: chr10-81371984; COSMIC: COSV64866838; COSMIC: COSV64866838;