6-25600740-G-A

Position:

• chr6-25600740-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017640.6(CARMIL1):​c.3546G>A​(p.Ala1182=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,518,214 control chromosomes in the GnomAD database, including 145,253 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 0.41 (13250 hom., cov: 32)
  • Exomes 𝑓: 0.44 (132003 hom.)
• Consequence: CARMIL1 NM_017640.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

Genes affected

CARMIL1 (HGNC:21581): (capping protein regulator and myosin 1 linker 1) Involved in several processes, including actin filament network formation; plasma membrane bounded cell projection organization; and positive regulation of cellular component organization. Located in several cellular components, including lamellipodium; macropinosome; and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-1.6 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARMIL1	NM_017640.6	c.3546G>A	p.Ala1182=	synonymous_variant	33/37	ENST00000329474.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARMIL1	ENST00000329474.7	c.3546G>A	p.Ala1182=	synonymous_variant	33/37	1	NM_017640.6	P1
CARMIL1	ENST00000700669.1	c.3546G>A	p.Ala1182=	synonymous_variant	33/37
CARMIL1	ENST00000635618.1	c.2346G>A	p.Ala782=	synonymous_variant, NMD_transcript_variant	20/26	5

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62772 AN: 151862 Hom.: 13241 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.399

GnomAD3 exomes AF: 0.434 AC: 69361 AN: 159654 Hom.: 14861 AF XY: 0.439 AC XY: 37161 AN XY: 84670

Gnomad AFR exome AF: 0.363

Gnomad AMR exome AF: 0.402

Gnomad ASJ exome AF: 0.455

Gnomad EAS exome AF: 0.374

Gnomad SAS exome AF: 0.462

Gnomad FIN exome AF: 0.408

Gnomad NFE exome AF: 0.463

Gnomad OTH exome AF: 0.447

GnomAD4 exome AF: 0.438 AC: 598105 AN: 1366232 Hom.: 132003 Cov.: 36 AF XY: 0.439 AC XY: 294459 AN XY: 670360

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.395

Gnomad4 ASJ exome AF: 0.445

Gnomad4 EAS exome AF: 0.335

Gnomad4 SAS exome AF: 0.445

Gnomad4 FIN exome AF: 0.406

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.434

GnomAD4 genome AF: 0.413 AC: 62815 AN: 151982 Hom.: 13250 Cov.: 32 AF XY: 0.410 AC XY: 30435 AN XY: 74290

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.404

Alfa AF: 0.449 Hom.: 29191

Bravo AF: 0.411

Asia WGS AF: 0.463 AC: 1610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.37
DANN	Benign	0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs10456324; hg19: chr6-25600968; COSMIC: COSV61516324;