10-79611798-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• 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 GnomAd at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPA1	NM_005411.5	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	c.-23-5T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_005411.5	P1

Frequencies

GnomAD3 genomes AF: 0.00848 AC: 1048 AN: 123628 Hom.: 13 Cov.: 33

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.: 1 Cov.: 105 AF XY: 0.000576 AC XY: 383 AN XY: 664634

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.: 13 Cov.: 33 AF XY: 0.00839 AC XY: 508 AN XY: 60530

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.: 0

ClinVar

Not reported in ClinVar

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

Other links and lift over

dbSNP: rs3997775; hg19: chr10-81371554;