Variant chr10-79611798-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_005411.5(SFTPA1):c.-23-5T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,461,868 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0085 ( 13 hom., cov: 33)

Exomes 𝑓: 0.00066 ( 1 hom. )

Consequence

SFTPA1
NM_005411.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.03134

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.30

Variant links:

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]

SFTPA1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 10-79611798-T-G is Benign according to our data. Variant chr10-79611798-T-G is described in ClinVar as [Benign]. Clinvar id is 3350749.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00853 (1055/123736) while in subpopulation AFR AF= 0.0281 (1001/35560). AF 95% confidence interval is 0.0267. There are 13 homozygotes in gnomad4. There are 508 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPA1	NM_005411.5 linkuse as main transcript	c.-23-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000398636.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPA1	ENST00000398636.8 linkuse as main transcript	c.-23-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_005411.5	P1	Q8IWL2-1

Frequencies

GnomAD3 genomes

AF:

0.00848

AC:

1048

AN:

123628

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0280

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00228

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000484

Gnomad SAS

AF:

0.000261

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00800

Gnomad NFE

AF:

0.000148

Gnomad OTH

AF:

0.00777

GnomAD4 exome

AF:

0.000663

AC:

887

AN:

1338132

Hom.:

Cov.:

105

AF XY:

0.000576

AC XY:

383

AN XY:

664634

show subpopulations

Gnomad4 AFR exome

AF:

0.0224

Gnomad4 AMR exome

AF:

0.00131

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000102

Gnomad4 FIN exome

AF:

0.0000213

Gnomad4 NFE exome

AF:

0.0000459

Gnomad4 OTH exome

AF:

0.00148

GnomAD4 genome

AF:

0.00853

AC:

1055

AN:

123736

Hom.:

Cov.:

AF XY:

0.00839

AC XY:

508

AN XY:

60530

show subpopulations

Gnomad4 AFR

AF:

0.0281

Gnomad4 AMR

AF:

0.00228

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000484

Gnomad4 SAS

AF:

0.000262

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000148

Gnomad4 OTH

AF:

0.00767

Alfa

AF:

0.000304

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SFTPA1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 02, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.1

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.031

dbscSNV1_RF

Benign

0.24

SpliceAI score (max)

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over