10-79615230-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005411.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPA1	NM_005411.5	MANE Select	c.*1117T>C		3_prime_UTR	Exon 6 of 6	NP_005402.3
	SFTPA1	NM_001093770.3		c.*1117T>C		3_prime_UTR	Exon 6 of 6	NP_001087239.2
	SFTPA1	NM_001164644.2		c.*1117T>C		3_prime_UTR	Exon 6 of 6	NP_001158116.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPA1	ENST00000398636.8	TSL:1 MANE Select	c.*1117T>C		3_prime_UTR	Exon 6 of 6	ENSP00000381633.3
	SFTPA1	ENST00000419470.6	TSL:1	c.*1117T>C		3_prime_UTR	Exon 6 of 6	ENSP00000397082.2
	SFTPA1	ENST00000428376.6	TSL:1	c.*1117T>C		3_prime_UTR	Exon 5 of 5	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

African (AFR) AF: 0.575 AC: 3946 AN: 6860

American (AMR) AF: 0.513 AC: 4170 AN: 8128

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 2405 AN: 4570

East Asian (EAS) AF: 0.776 AC: 5760 AN: 7426

South Asian (SAS) AF: 0.609 AC: 21957 AN: 36072

European-Finnish (FIN) AF: 0.419 AC: 9701 AN: 23174

Middle Eastern (MID) AF: 0.521 AC: 463 AN: 888

European-Non Finnish (NFE) AF: 0.370 AC: 78153 AN: 210978

Other (OTH) AF: 0.446 AC: 5416 AN: 12156

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

African (AFR) AF: 0.570 AC: 23642 AN: 41458

American (AMR) AF: 0.522 AC: 7973 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1838 AN: 3468

East Asian (EAS) AF: 0.755 AC: 3892 AN: 5154

South Asian (SAS) AF: 0.627 AC: 3013 AN: 4808

European-Finnish (FIN) AF: 0.398 AC: 4194 AN: 10546

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26766 AN: 67976

Other (OTH) AF: 0.509 AC: 1074 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.77
PhyloP100		-0.074
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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