rs4740951

Variant names:

• chr9-864834-A-G
• rs4740951
• NM_021951.3:c.538+17691A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-864834-A-G
• chr9-864834-A-T

Variant summary

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

The NM_021951.3(DMRT1):​c.538+17691A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0651 in 151,132 control chromosomes in the GnomAD database, including 648 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 0.065 (648 hom., cov: 34)
• Consequence: DMRT1 NM_021951.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 0 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021951.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMRT1	NM_021951.3	MANE Select	c.538+17691A>G		intron	N/A	NP_068770.2	Q9Y5R6-1
	DMRT1	NM_001363767.1		c.64+17691A>G		intron	N/A	NP_001350696.1	H3BN61

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMRT1	ENST00000382276.8	TSL:1 MANE Select	c.538+17691A>G		intron	N/A	ENSP00000371711.3	Q9Y5R6-1
	DMRT1	ENST00000569227.1	TSL:1	c.64+17691A>G		intron	N/A	ENSP00000454701.1	H3BN61
	DMRT1	ENST00000564322.1	TSL:1	n.687+17691A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9814 AN: 151014 Hom.: 643 Cov.: 34

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.0347

Gnomad FIN AF: 0.0944

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00928

Gnomad OTH AF: 0.0629

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

GnomAD4 genome AF: 0.0651 AC: 9843 AN: 151132 Hom.: 648 Cov.: 34 AF XY: 0.0725 AC XY: 5349 AN XY: 73772

African (AFR) AF: 0.105 AC: 4329 AN: 41086

American (AMR) AF: 0.163 AC: 2459 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3462

East Asian (EAS) AF: 0.214 AC: 1092 AN: 5114

South Asian (SAS) AF: 0.0343 AC: 162 AN: 4728

European-Finnish (FIN) AF: 0.0944 AC: 987 AN: 10454

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00927 AC: 629 AN: 67884

Other (OTH) AF: 0.0632 AC: 131 AN: 2072

Alfa AF: 0.0388 Hom.: 34

Bravo AF: 0.0757

Asia WGS AF: 0.118 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.40
DANN	Benign	0.60
PhyloP100		-1.4
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: rs4740951; hg19: chr9-864834;