rs1650223

Variant names:

• chr10-79612228-T-C
• rs1650223
• NM_005411.5:c.173-84T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005411.5(SFTPA1):​c.173-84T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000402 in 1,610,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (0 hom.)
• Consequence: SFTPA1 NM_005411.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.55
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPA1	NM_005411.5	c.173-84T>C		intron_variant	Intron 3 of 5	ENST00000398636.8	NP_005402.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPA1	ENST00000398636.8	c.173-84T>C		intron_variant	Intron 3 of 5	1	NM_005411.5	ENSP00000381633.3
SFTPA1	ENST00000419470.6	c.218-84T>C		intron_variant	Intron 3 of 5	1		ENSP00000397082.2
SFTPA1	ENST00000428376.6	c.173-84T>C		intron_variant	Intron 2 of 4	1		ENSP00000411102.2
SFTPA1	ENST00000429958.5	c.173-84T>C		intron_variant	Intron 2 of 4	1		ENSP00000395527.1

Frequencies

GnomAD3 genomes AF: 0.000375 AC: 57 AN: 152082 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.000956

GnomAD4 exome AF: 0.000405 AC: 591 AN: 1458206 Hom.: 0 AF XY: 0.000412 AC XY: 299 AN XY: 725510

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

African (AFR) AF: 0.000509 AC: 17 AN: 33392

American (AMR) AF: 0.000336 AC: 15 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00111 AC: 44 AN: 39666

South Asian (SAS) AF: 0.000630 AC: 54 AN: 85728

European-Finnish (FIN) AF: 0.000281 AC: 15 AN: 53354

Middle Eastern (MID) AF: 0.000591 AC: 3 AN: 5074

European-Non Finnish (NFE) AF: 0.000376 AC: 417 AN: 1109950

Other (OTH) AF: 0.000432 AC: 26 AN: 60228

⚠️ 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: 0.000375 AC: 57 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24 AN XY: 74410

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

African (AFR) AF: 0.000602 AC: 25 AN: 41538

American (AMR) AF: 0.000131 AC: 2 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000324 AC: 22 AN: 67962

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000612 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.040
DANN	Benign	0.13
PhyloP100		-4.5
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1650223; hg19: chr10-81371984; COSMIC: COSV64866838; COSMIC: COSV64866838;