10-79612689-T-C

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.292+258T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,320 control chromosomes in the GnomAD database, including 3,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (3847 hom., cov: 31)
• Consequence: SFTPA1 NM_005411.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.69

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=-0.89).
• BP6: Variant 10-79612689-T-C is Benign according to our data. Variant chr10-79612689-T-C is described in ClinVar as [Benign]. Clinvar id is 1235406.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPA1	NM_005411.5	c.292+258T>C		intron_variant		ENST00000398636.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPA1	ENST00000398636.8	c.292+258T>C		intron_variant		1	NM_005411.5	P1
SFTPA1	ENST00000419470.6	c.337+258T>C		intron_variant		1
SFTPA1	ENST00000428376.6	c.292+258T>C		intron_variant		1		P1
SFTPA1	ENST00000429958.5	c.292+258T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32684 AN: 151198 Hom.: 3840 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.225

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.216 AC: 32727 AN: 151320 Hom.: 3847 Cov.: 31 AF XY: 0.219 AC XY: 16196 AN XY: 73942

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.225

Alfa AF: 0.216 Hom.: 459

Bravo AF: 0.210

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.010
Dann	Benign	0.43

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: rs4253515; hg19: chr10-81372445;