rs7040024

Variant names:

• chr9-845516-A-C
• rs7040024
• NM_021951.3:c.355-1444A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-845516-A-C
• chr9-845516-A-G
• chr9-845516-A-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_021951.3(DMRT1):​c.355-1444A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 151,914 control chromosomes in the GnomAD database, including 4,733 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 0.25 (4733 hom., cov: 32)
• Consequence: DMRT1 NM_021951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248
• Publications: 27 publications found

Genes affected

DMRT1 (HGNC:2934): (doublesex and mab-3 related transcription factor 1) This gene is found in a cluster with two other members of the gene family, having in common a zinc finger-like DNA-binding motif (DM domain). The DM domain is an ancient, conserved component of the vertebrate sex-determining pathway that is also a key regulator of male development in flies and nematodes. This gene exhibits a gonad-specific and sexually dimorphic expression pattern. Defective testicular development and XY feminization occur when this gene is hemizygous. [provided by RefSeq, Jul 2008]

DMRT1 Gene-Disease associations (from GenCC):

• 46,XY disorder of sex development

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• 46,XX disorder of sex development

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000294371 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMRT1	NM_021951.3	c.355-1444A>C		intron_variant	Intron 1 of 4	ENST00000382276.8	NP_068770.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMRT1	ENST00000382276.8	c.355-1444A>C		intron_variant	Intron 1 of 4	1	NM_021951.3	ENSP00000371711.3
DMRT1	ENST00000569227.1	c.-120-1444A>C		intron_variant	Intron 1 of 4	1		ENSP00000454701.1
DMRT1	ENST00000564322.1	n.504-1444A>C		intron_variant	Intron 1 of 2	1
ENSG00000294371	ENST00000723200.1	n.401+1339T>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37627 AN: 151796 Hom.: 4723 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.248 AC: 37676 AN: 151914 Hom.: 4733 Cov.: 32 AF XY: 0.249 AC XY: 18513 AN XY: 74262

African (AFR) AF: 0.253 AC: 10475 AN: 41448

American (AMR) AF: 0.248 AC: 3785 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 849 AN: 3468

East Asian (EAS) AF: 0.168 AC: 868 AN: 5152

South Asian (SAS) AF: 0.218 AC: 1048 AN: 4804

European-Finnish (FIN) AF: 0.307 AC: 3231 AN: 10538

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16560 AN: 67942

Other (OTH) AF: 0.240 AC: 504 AN: 2104

Alfa AF: 0.245 Hom.: 18166

Bravo AF: 0.247

Asia WGS AF: 0.202 AC: 701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	5.1
DANN	Benign	0.86
PhyloP100		0.25
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: rs7040024; hg19: chr9-845516; COSMIC: COSV66523967;