10-79612475-CG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005411.5(SFTPA1):c.292+45del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,608,504 control chromosomes in the GnomAD database, including 37,694 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3539 hom., cov: 26)
  • Exomes 𝑓: 0.21 (34155 hom.)
• Consequence: SFTPA1 NM_005411.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.188

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 -10 ACMG points.

• BP6: Variant 10-79612475-CG-C is Benign according to our data. Variant chr10-79612475-CG-C is described in ClinVar as [Benign]. Clinvar id is 1270909.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPA1	NM_005411.5	c.292+45del		intron_variant		ENST00000398636.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPA1	ENST00000398636.8	c.292+45del		intron_variant		1	NM_005411.5	P1
SFTPA1	ENST00000419470.6	c.337+45del		intron_variant		1
SFTPA1	ENST00000428376.6	c.292+45del		intron_variant		1		P1
SFTPA1	ENST00000429958.5	c.292+45del		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31516 AN: 151866 Hom.: 3532 Cov.: 26

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.216

GnomAD3 exomes AF: 0.231 AC: 57731 AN: 249618 Hom.: 7482 AF XY: 0.240 AC XY: 32382 AN XY: 135008

Gnomad AFR exome AF: 0.186

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.262

Gnomad EAS exome AF: 0.467

Gnomad SAS exome AF: 0.345

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.191

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.207 AC: 301173 AN: 1456522 Hom.: 34155 Cov.: 30 AF XY: 0.212 AC XY: 153757 AN XY: 724640

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.458

Gnomad4 SAS exome AF: 0.347

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.219

GnomAD4 genome AF: 0.208 AC: 31557 AN: 151982 Hom.: 3539 Cov.: 26 AF XY: 0.211 AC XY: 15668 AN XY: 74278

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.216

Alfa AF: 0.149 Hom.: 409

Bravo AF: 0.200

Asia WGS AF: 0.392 AC: 1362 AN: 3478

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

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: rs4253514; hg19: chr10-81372231; COSMIC: COSV64866867; COSMIC: COSV64866867;