10-79947217-C-T

Variant names:

• chr10-79947217-C-T
• rs726288
• NM_003019.5:c.-3-555G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003019.5(SFTPD):​c.-3-555G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0328 in 152,322 control chromosomes in the GnomAD database, including 188 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 0.033 (188 hom., cov: 33)
• Consequence: SFTPD NM_003019.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPD	NM_003019.5	c.-3-555G>A		intron_variant	Intron 1 of 7	ENST00000372292.8	NP_003010.4
SFTPD	XM_011540087.2	c.-3-555G>A		intron_variant	Intron 1 of 7		XP_011538389.1
SFTPD	XM_011540088.3	c.-3-555G>A		intron_variant	Intron 1 of 6		XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPD	ENST00000372292.8	c.-3-555G>A		intron_variant	Intron 1 of 7	1	NM_003019.5	ENSP00000361366.3

Frequencies

GnomAD3 genomes AF: 0.0329 AC: 5001 AN: 152204 Hom.: 189 Cov.: 33

Gnomad AFR AF: 0.00526

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0307

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.0940

Gnomad FIN AF: 0.0134

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0323

Gnomad OTH AF: 0.0363

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

GnomAD4 genome AF: 0.0328 AC: 4997 AN: 152322 Hom.: 188 Cov.: 33 AF XY: 0.0347 AC XY: 2585 AN XY: 74482

African (AFR) AF: 0.00522 AC: 217 AN: 41564

American (AMR) AF: 0.0306 AC: 469 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 251 AN: 3472

East Asian (EAS) AF: 0.217 AC: 1125 AN: 5182

South Asian (SAS) AF: 0.0942 AC: 455 AN: 4828

European-Finnish (FIN) AF: 0.0134 AC: 142 AN: 10620

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0323 AC: 2195 AN: 68030

Other (OTH) AF: 0.0374 AC: 79 AN: 2114

Alfa AF: 0.0338 Hom.: 275

Bravo AF: 0.0325

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.72
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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: rs726288; hg19: chr10-81706973;