rs12770776

Positions:

• chr10-79949788-A-G

Variant summary

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

The ENST00000444384.3(SFTPD):​c.37-3126T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0294 in 151,624 control chromosomes in the GnomAD database, including 93 homozygotes. 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 0.029 (93 hom., cov: 32)
• Consequence: SFTPD ENST00000444384.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182

Genes affected

SFTPD (HGNC:10803): (surfactant protein D) The protein encoded by this gene is part of the innate immune response, protecting the lungs against inhaled microorganisms and chemicals. The encoded protein may also be involved in surfactant metabolism. [provided by RefSeq, Jul 2015]

ENSG00000283913 (HGNC:):

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 nfe. gnomad4 allele frequency = 0.0294 (4454/151624) while in subpopulation NFE AF= 0.0438 (2980/67984). AF 95% confidence interval is 0.0425. There are 93 homozygotes in gnomad4. There are 2172 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 93 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPD	XM_011540087.2	c.-3-3126T>C		intron_variant			XP_011538389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPD	ENST00000444384.3	c.37-3126T>C		intron_variant		3		ENSP00000394325.1
ENSG00000283913	ENST00000421889.1	n.334-240A>G		intron_variant		3
ENSG00000283913	ENST00000453174.7	n.962-240A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0294 AC: 4449 AN: 151576 Hom.: 92 Cov.: 32

Gnomad AFR AF: 0.00701

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0267

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0270

Gnomad FIN AF: 0.0473

Gnomad MID AF: 0.0195

Gnomad NFE AF: 0.0438

Gnomad OTH AF: 0.0275

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

GnomAD4 genome AF: 0.0294 AC: 4454 AN: 151624 Hom.: 93 Cov.: 32 AF XY: 0.0294 AC XY: 2172 AN XY: 73992

Gnomad4 AFR AF: 0.00700

Gnomad4 AMR AF: 0.0267

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.000968

Gnomad4 SAS AF: 0.0282

Gnomad4 FIN AF: 0.0473

Gnomad4 NFE AF: 0.0438

Gnomad4 OTH AF: 0.0272

Alfa AF: 0.0387 Hom.: 156

Bravo AF: 0.0259

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.93
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12770776; hg19: chr10-81709544;