10-79615230-T-C

Variant names:

• chr10-79615230-T-C
• rs1059225
• NM_005411.5:c.*1117T>C

Variant summary

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

The NM_005411.5(SFTPA1):​c.*1117T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 462,256 control chromosomes in the GnomAD database, including 48,734 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 0.48 (18292 hom., cov: 31)
  • Exomes 𝑓: 0.43 (30442 hom.)
• Consequence: SFTPA1 NM_005411.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA1	NM_005411.5	c.*1117T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000398636.8	NP_005402.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPA1	ENST00000398636.8	c.*1117T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_005411.5	ENSP00000381633.3
SFTPA1	ENST00000419470.6	c.*1117T>C		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000397082.2
SFTPA1	ENST00000428376.6	c.*1117T>C		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000411102.2

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72663 AN: 151886 Hom.: 18237 Cov.: 31

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.505

GnomAD4 exome AF: 0.425 AC: 131971 AN: 310252 Hom.: 30442 Cov.: 6 AF XY: 0.440 AC XY: 70743 AN XY: 160956

Gnomad4 AFR exome AF: 0.575

Gnomad4 AMR exome AF: 0.513

Gnomad4 ASJ exome AF: 0.526

Gnomad4 EAS exome AF: 0.776

Gnomad4 SAS exome AF: 0.609

Gnomad4 FIN exome AF: 0.419

Gnomad4 NFE exome AF: 0.370

Gnomad4 OTH exome AF: 0.446

GnomAD4 genome AF: 0.479 AC: 72785 AN: 152004 Hom.: 18292 Cov.: 31 AF XY: 0.485 AC XY: 36038 AN XY: 74294

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.509

Alfa AF: 0.455 Hom.: 2070

Bravo AF: 0.488

Asia WGS AF: 0.721 AC: 2505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.77

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: rs1059225; hg19: chr10-81374986; COSMIC: COSV64867728; COSMIC: COSV64867728;