rs6938281

Variant names:

• chr6-25312260-A-G
• rs6938281
• NM_017640.6:c.138+27351A>G

Variant summary

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

The NM_017640.6(CARMIL1):​c.138+27351A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,114 control chromosomes in the GnomAD database, including 4,232 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 0.21 (4232 hom., cov: 32)
• Consequence: CARMIL1 NM_017640.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206
• Publications: 1 publications found

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]

CMAHP (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARMIL1	NM_017640.6	c.138+27351A>G		intron_variant	Intron 2 of 36	ENST00000329474.7	NP_060110.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARMIL1	ENST00000329474.7	c.138+27351A>G		intron_variant	Intron 2 of 36	1	NM_017640.6	ENSP00000331983.6

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31561 AN: 151994 Hom.: 4221 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.0916

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.208 AC: 31620 AN: 152114 Hom.: 4232 Cov.: 32 AF XY: 0.211 AC XY: 15693 AN XY: 74368

African (AFR) AF: 0.359 AC: 14890 AN: 41440

American (AMR) AF: 0.182 AC: 2788 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3470

East Asian (EAS) AF: 0.399 AC: 2063 AN: 5164

South Asian (SAS) AF: 0.290 AC: 1397 AN: 4814

European-Finnish (FIN) AF: 0.0916 AC: 972 AN: 10608

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8254 AN: 67998

Other (OTH) AF: 0.228 AC: 481 AN: 2114

Alfa AF: 0.173 Hom.: 407

Bravo AF: 0.218

Asia WGS AF: 0.310 AC: 1076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.43
PhyloP100		-0.21
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: rs6938281; hg19: chr6-25312488;