rs1231128

Variant names:

• chr11-75587752-A-G
• rs1231128
• NM_033063.2:c.1749T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-75587752-A-G
• chr11-75587752-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_033063.2(MAP6):​c.1749T>C​(p.Asp583Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,613,716 control chromosomes in the GnomAD database, including 88,516 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (8735 hom., cov: 31)
  • Exomes 𝑓: 0.32 (79781 hom.)
• Consequence: MAP6 NM_033063.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.795
• Publications: 16 publications found

Genes affected

MAP6 (HGNC:6868): (microtubule associated protein 6) This gene encodes a microtubule-associated protein. The encoded protein is a calmodulin-binding and calmodulin-regulated protein that is involved in microtubule stabilization. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

MAP6-AS1 (HGNC:58170):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-75587752-A-G is Benign according to our data. Variant chr11-75587752-A-G is described in ClinVar as Benign. ClinVar VariationId is 1289911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.795 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033063.2. 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
	MAP6	NM_033063.2	MANE Select	c.1749T>C	p.Asp583Asp	synonymous	Exon 4 of 4	NP_149052.1	Q96JE9-1
	MAP6-AS1	NR_145823.1		n.86+4471A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP6	ENST00000304771.8	TSL:1 MANE Select	c.1749T>C	p.Asp583Asp	synonymous	Exon 4 of 4	ENSP00000307093.3	Q96JE9-1
	MAP6	ENST00000950404.1		c.1788T>C	p.Asp596Asp	synonymous	Exon 5 of 5	ENSP00000620463.1
	MAP6	ENST00000950405.1		c.1338T>C	p.Asp446Asp	synonymous	Exon 2 of 2	ENSP00000620464.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50179 AN: 151774 Hom.: 8704 Cov.: 31

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.332

GnomAD2 exomes AF: 0.369 AC: 92803 AN: 251464 AF XY: 0.366

Gnomad AFR exome AF: 0.293

Gnomad AMR exome AF: 0.624

Gnomad ASJ exome AF: 0.346

Gnomad EAS exome AF: 0.235

Gnomad FIN exome AF: 0.346

Gnomad NFE exome AF: 0.306

Gnomad OTH exome AF: 0.347

GnomAD4 exome AF: 0.322 AC: 471125 AN: 1461824 Hom.: 79781 Cov.: 57 AF XY: 0.325 AC XY: 236517 AN XY: 727220

African (AFR) AF: 0.297 AC: 9929 AN: 33480

American (AMR) AF: 0.613 AC: 27415 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 9002 AN: 26124

East Asian (EAS) AF: 0.253 AC: 10061 AN: 39698

South Asian (SAS) AF: 0.456 AC: 39294 AN: 86250

European-Finnish (FIN) AF: 0.343 AC: 18314 AN: 53420

Middle Eastern (MID) AF: 0.307 AC: 1766 AN: 5746

European-Non Finnish (NFE) AF: 0.302 AC: 335635 AN: 1111992

Other (OTH) AF: 0.326 AC: 19709 AN: 60390

GnomAD4 genome AF: 0.331 AC: 50252 AN: 151892 Hom.: 8735 Cov.: 31 AF XY: 0.340 AC XY: 25224 AN XY: 74240

African (AFR) AF: 0.297 AC: 12305 AN: 41394

American (AMR) AF: 0.491 AC: 7504 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1211 AN: 3462

East Asian (EAS) AF: 0.246 AC: 1270 AN: 5154

South Asian (SAS) AF: 0.475 AC: 2275 AN: 4794

European-Finnish (FIN) AF: 0.359 AC: 3797 AN: 10574

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20704 AN: 67932

Other (OTH) AF: 0.337 AC: 711 AN: 2108

Alfa AF: 0.315 Hom.: 4553

Bravo AF: 0.340

Asia WGS AF: 0.406 AC: 1410 AN: 3478

EpiCase AF: 0.320

EpiControl AF: 0.303

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.21
DANN	Benign	0.81
PhyloP100		-0.80
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: rs1231128; hg19: chr11-75298797; COSMIC: COSV59076536; COSMIC: COSV59076536;