rs1136454

chr10-79612421-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_005411.5(SFTPA1):c.282G>A(p.Arg94=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,612,532 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 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: SFTPA1 NM_005411.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376

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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-0.376 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPA1	NM_005411.5	c.282G>A	p.Arg94=	synonymous_variant	4/6	ENST00000398636.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPA1	ENST00000398636.8	c.282G>A	p.Arg94=	synonymous_variant	4/6	1	NM_005411.5	P1
SFTPA1	ENST00000419470.6	c.327G>A	p.Arg109=	synonymous_variant	4/6	1
SFTPA1	ENST00000428376.6	c.282G>A	p.Arg94=	synonymous_variant	3/5	1		P1
SFTPA1	ENST00000429958.5	c.282G>A	p.Arg94=	synonymous_variant	3/5	1

Frequencies

GnomAD3 genomes AF: 0.0000659 AC: 10 AN: 151780 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000833

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00133 AC: 321 AN: 241782 Hom.: 0 AF XY: 0.00136 AC XY: 178 AN XY: 130486

Gnomad AFR exome AF: 0.000444

Gnomad AMR exome AF: 0.000206

Gnomad ASJ exome AF: 0.00422

Gnomad EAS exome AF: 0.00178

Gnomad SAS exome AF: 0.00238

Gnomad FIN exome AF: 0.000807

Gnomad NFE exome AF: 0.00132

Gnomad OTH exome AF: 0.00101

GnomAD4 exome AF: 0.000107 AC: 157 AN: 1460628 Hom.: 0 Cov.: 34 AF XY: 0.0000991 AC XY: 72 AN XY: 726624

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000936

Gnomad4 OTH exome AF: 0.000332

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 151904 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74256

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000833

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000589

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0108 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	5.4
Dann	Benign	0.66

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: rs1136454; hg19: chr10-81372177; COSMIC: COSV64866694; COSMIC: COSV64866694;