rs61753093

Variant names:

• chr7-2538327-C-A
• rs61753093
• NM_152743.4:c.2208G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-2538327-C-A
• chr7-2538327-C-G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_152743.4(BRAT1):​c.2208G>T​(p.Leu736Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,613,090 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L736L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 34)
  • Exomes 𝑓: 0.0026 (13 hom.)
• Consequence: BRAT1 NM_152743.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.431
• Publications: 2 publications found

Genes affected

BRAT1 (HGNC:21701): (BRCA1 associated ATM activator 1) The protein encoded by this ubiquitously expressed gene interacts with the tumor suppressing BRCA1 (breast cancer 1) protein and and the ATM (ataxia telangiectasia mutated) protein. ATM is thought to be a master controller of cell cycle checkpoint signalling pathways that are required for cellular responses to DNA damage such as double-strand breaks that are induced by ionizing radiation and complexes with BRCA1 in the multi-protein complex BASC (BRAC1-associated genome surveillance complex). The protein encoded by this gene is thought to play a role in the DNA damage pathway regulated by BRCA1 and ATM. [provided by RefSeq, Mar 2012]

BRAT1 Gene-Disease associations (from GenCC):

• neonatal-onset encephalopathy with rigidity and seizures

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• neurodevelopmental disorder with cerebellar atrophy and with or without seizures

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 7-2538327-C-A is Benign according to our data. Variant chr7-2538327-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 472963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.431 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152743.4. 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
	BRAT1	NM_152743.4	MANE Select	c.2208G>T	p.Leu736Leu	synonymous	Exon 14 of 14	NP_689956.2	Q6PJG6-1
	BRAT1	NM_001350626.2		c.2388G>T	p.Leu796Leu	synonymous	Exon 14 of 14	NP_001337555.1
	BRAT1	NM_001350627.2		c.1683G>T	p.Leu561Leu	synonymous	Exon 13 of 13	NP_001337556.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRAT1	ENST00000340611.9	TSL:1 MANE Select	c.2208G>T	p.Leu736Leu	synonymous	Exon 14 of 14	ENSP00000339637.4	Q6PJG6-1
	BRAT1	ENST00000890463.1		c.2445G>T	p.Leu815Leu	synonymous	Exon 16 of 16	ENSP00000560522.1
	BRAT1	ENST00000917322.1		c.2442G>T	p.Leu814Leu	synonymous	Exon 16 of 16	ENSP00000587381.1

Frequencies

GnomAD3 genomes AF: 0.00184 AC: 280 AN: 152216 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00930

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00245

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00259 AC: 644 AN: 248466 AF XY: 0.00287

Gnomad AFR exome AF: 0.000312

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00569

Gnomad EAS exome AF: 0.0000553

Gnomad FIN exome AF: 0.000372

Gnomad NFE exome AF: 0.00281

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00262 AC: 3826 AN: 1460756 Hom.: 13 Cov.: 66 AF XY: 0.00273 AC XY: 1986 AN XY: 726700

African (AFR) AF: 0.000299 AC: 10 AN: 33472

American (AMR) AF: 0.00136 AC: 61 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00528 AC: 138 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00652 AC: 562 AN: 86258

European-Finnish (FIN) AF: 0.000286 AC: 15 AN: 52452

Middle Eastern (MID) AF: 0.00381 AC: 22 AN: 5768

European-Non Finnish (NFE) AF: 0.00257 AC: 2859 AN: 1111896

Other (OTH) AF: 0.00263 AC: 159 AN: 60370

GnomAD4 genome AF: 0.00184 AC: 281 AN: 152334 Hom.: 1 Cov.: 34 AF XY: 0.00203 AC XY: 151 AN XY: 74506

African (AFR) AF: 0.000313 AC: 13 AN: 41578

American (AMR) AF: 0.00196 AC: 30 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00952 AC: 46 AN: 4834

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00246 AC: 167 AN: 68024

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00238 Hom.: 0

Bravo AF: 0.00163

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.00273

EpiControl AF: 0.00373

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not provided (6)
-	-	1	BRAT1-related disorder (1)
-	-	1	Neonatal-onset encephalopathy with rigidity and seizures (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.18
DANN	Benign	0.51
PhyloP100		-0.43
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: rs61753093; hg19: chr7-2577961;