rs6902158

Positions:

• chr6-25561402-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017640.6(CARMIL1):​c.2742+4552G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,110 control chromosomes in the GnomAD database, including 1,647 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 0.14 (1647 hom., cov: 32)
• Consequence: CARMIL1 NM_017640.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARMIL1	NM_017640.6	c.2742+4552G>A		intron_variant		ENST00000329474.7	NP_060110.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARMIL1	ENST00000329474.7	c.2742+4552G>A		intron_variant		1	NM_017640.6	ENSP00000331983	P1
CARMIL1	ENST00000700669.1	c.2742+4552G>A		intron_variant				ENSP00000515137
CARMIL1	ENST00000635618.1	c.1524+4552G>A		intron_variant, NMD_transcript_variant		5		ENSP00000489114

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21509 AN: 151992 Hom.: 1645 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0588

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.141 AC: 21518 AN: 152110 Hom.: 1647 Cov.: 32 AF XY: 0.142 AC XY: 10595 AN XY: 74358

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.0586

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.129

Alfa AF: 0.153 Hom.: 443

Bravo AF: 0.136

Asia WGS AF: 0.101 AC: 353 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.79

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: rs6902158; hg19: chr6-25561630;