10-79611665-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005411.5(SFTPA1):c.-23-138A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.088 in 1,552,272 control chromosomes in the GnomAD database, including 7,473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1087 hom., cov: 33)
  • Exomes 𝑓: 0.085 (6386 hom.)
• Consequence: SFTPA1 NM_005411.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.22

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 10-79611665-A-T is Benign according to our data. Variant chr10-79611665-A-T is described in ClinVar as [Benign]. Clinvar id is 1260769.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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	UniProt
SFTPA1	NM_005411.5	c.-23-138A>T		intron_variant		ENST00000398636.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPA1	ENST00000398636.8	c.-23-138A>T		intron_variant		1	NM_005411.5	P1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16939 AN: 151912 Hom.: 1087 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.0740

Gnomad FIN AF: 0.0980

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0877

Gnomad OTH AF: 0.129

GnomAD3 exomes AF: 0.0825 AC: 14492 AN: 175766 Hom.: 972 AF XY: 0.0784 AC XY: 7374 AN XY: 94106

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.0756

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.233

Gnomad SAS exome AF: 0.0439

Gnomad FIN exome AF: 0.0828

Gnomad NFE exome AF: 0.0647

Gnomad OTH exome AF: 0.0859

GnomAD4 exome AF: 0.0855 AC: 119703 AN: 1400242 Hom.: 6386 Cov.: 32 AF XY: 0.0845 AC XY: 58461 AN XY: 692188

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.0913

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.0611

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.0781

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.112 AC: 16967 AN: 152030 Hom.: 1087 Cov.: 33 AF XY: 0.113 AC XY: 8411 AN XY: 74306

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.0743

Gnomad4 FIN AF: 0.0980

Gnomad4 NFE AF: 0.0877

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0990 Hom.: 144

Bravo AF: 0.115

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.1
Dann	Benign	0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2678553; hg19: chr10-81371421; COSMIC: COSV64867678;