10-79946452-C-T

Variant names:

• chr10-79946452-C-T
• rs6413522
• NM_003019.5:c.199+9G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_003019.5(SFTPD):​c.199+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,609,382 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (20 hom.)
• Consequence: SFTPD NM_003019.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.563
• Publications: 1 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-79946452-C-T is Benign according to our data. Variant chr10-79946452-C-T is described in ClinVar as Benign. ClinVar VariationId is 227074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPD	NM_003019.5	c.199+9G>A		intron_variant	Intron 2 of 7	ENST00000372292.8	NP_003010.4
SFTPD	XM_011540087.2	c.199+9G>A		intron_variant	Intron 2 of 7		XP_011538389.1
SFTPD	XM_011540088.3	c.199+9G>A		intron_variant	Intron 2 of 6		XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPD	ENST00000372292.8	c.199+9G>A		intron_variant	Intron 2 of 7	1	NM_003019.5	ENSP00000361366.3

Frequencies

GnomAD3 genomes AF: 0.00219 AC: 334 AN: 152230 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00973

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00272

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00338 AC: 846 AN: 250220 AF XY: 0.00398

Gnomad AFR exome AF: 0.000310

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.00756

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000472

Gnomad NFE exome AF: 0.00291

Gnomad OTH exome AF: 0.00574

GnomAD4 exome AF: 0.00310 AC: 4510 AN: 1457034 Hom.: 20 Cov.: 30 AF XY: 0.00335 AC XY: 2426 AN XY: 725106

African (AFR) AF: 0.000509 AC: 17 AN: 33386

American (AMR) AF: 0.00179 AC: 80 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00915 AC: 239 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.0114 AC: 985 AN: 86150

European-Finnish (FIN) AF: 0.000604 AC: 32 AN: 52988

Middle Eastern (MID) AF: 0.00661 AC: 38 AN: 5748

European-Non Finnish (NFE) AF: 0.00265 AC: 2938 AN: 1108056

Other (OTH) AF: 0.00301 AC: 181 AN: 60220

GnomAD4 genome AF: 0.00218 AC: 332 AN: 152348 Hom.: 1 Cov.: 33 AF XY: 0.00228 AC XY: 170 AN XY: 74494

African (AFR) AF: 0.000625 AC: 26 AN: 41592

American (AMR) AF: 0.00124 AC: 19 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 38 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00932 AC: 45 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00272 AC: 185 AN: 68032

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00234 Hom.: 1

Bravo AF: 0.00220

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

199+9G>A in intron 2 of SFTPD: This variant is not expected to have clinical sig nificance because it is not located within the conserved splice consensus sequen ce. It has been identified in 0.4% (32/8600) of European American chromosomes fr om a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washi ngton.edu/EVS; dbSNP rs6413522).

Sep 18, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Oct 05, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

SFTPD-related disorder Benign:1

Mar 05, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	16
DANN	Benign	0.73
PhyloP100		0.56
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: rs6413522; hg19: chr10-81706208;