10-79611665-A-T

Variant names:

• chr10-79611665-A-T
• rs2678553
• NM_005411.5:c.-23-138A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.22
• Publications: 5 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 -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
SFTPA1	NM_005411.5	c.-23-138A>T		intron_variant	Intron 2 of 5	ENST00000398636.8	NP_005402.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPA1	ENST00000398636.8	c.-23-138A>T		intron_variant	Intron 2 of 5	1	NM_005411.5	ENSP00000381633.3

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

GnomAD2 exomes AF: 0.0825 AC: 14492 AN: 175766 AF XY: 0.0784

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.132 AC: 4203 AN: 31876

American (AMR) AF: 0.0913 AC: 3315 AN: 36318

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 3439 AN: 24980

East Asian (EAS) AF: 0.219 AC: 8049 AN: 36678

South Asian (SAS) AF: 0.0611 AC: 4959 AN: 81140

European-Finnish (FIN) AF: 0.105 AC: 5276 AN: 50152

Middle Eastern (MID) AF: 0.104 AC: 507 AN: 4872

European-Non Finnish (NFE) AF: 0.0781 AC: 84013 AN: 1076248

Other (OTH) AF: 0.102 AC: 5942 AN: 57978

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.137 AC: 5689 AN: 41452

American (AMR) AF: 0.114 AC: 1749 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 512 AN: 3466

East Asian (EAS) AF: 0.240 AC: 1235 AN: 5140

South Asian (SAS) AF: 0.0743 AC: 357 AN: 4808

European-Finnish (FIN) AF: 0.0980 AC: 1038 AN: 10590

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0877 AC: 5960 AN: 67972

Other (OTH) AF: 0.131 AC: 278 AN: 2116

Alfa AF: 0.0990 Hom.: 144

Bravo AF: 0.115

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.23
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2678553; hg19: chr10-81371421; COSMIC: COSV64867678;