16-81620052-C-T

Variant names:

• chr16-81620052-C-T
• rs6564903
• NM_198390.3:c.427-824C>T

Variant summary

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

The NM_198390.3(CMIP):​c.427-824C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,026 control chromosomes in the GnomAD database, including 19,973 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 0.50 (19972 hom., cov: 32)
  • Exomes 𝑓: 0.43 (1 hom.)
• Consequence: CMIP NM_198390.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 19 publications found

Genes affected

CMIP (HGNC:24319): (c-Maf inducing protein) This gene encodes a c-Maf inducing protein that plays a role in T-cell signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

ENSG00000279294 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198390.3. 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
	CMIP	NM_198390.3	MANE Select	c.427-824C>T		intron	N/A	NP_938204.2	Q8IY22-1
	CMIP	NM_030629.3		c.145-824C>T		intron	N/A	NP_085132.1	Q8IY22-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMIP	ENST00000537098.8	TSL:1 MANE Select	c.427-824C>T		intron	N/A	ENSP00000446100.2	Q8IY22-1
	CMIP	ENST00000539778.6	TSL:1	c.145-824C>T		intron	N/A	ENSP00000440401.2	Q8IY22-2
	CMIP	ENST00000565029.5	TSL:1	n.235-824C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76643 AN: 151894 Hom.: 19945 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.518

GnomAD4 exome AF: 0.429 AC: 6 AN: 14 Hom.: 1 Cov.: 0 AF XY: 0.300 AC XY: 3 AN XY: 10

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.375 AC: 3 AN: 8

Other (OTH) AF: 0.00 AC: 0 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0942227), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.505 AC: 76718 AN: 152012 Hom.: 19972 Cov.: 32 AF XY: 0.506 AC XY: 37575 AN XY: 74272

African (AFR) AF: 0.545 AC: 22587 AN: 41454

American (AMR) AF: 0.552 AC: 8440 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1665 AN: 3470

East Asian (EAS) AF: 0.787 AC: 4071 AN: 5174

South Asian (SAS) AF: 0.482 AC: 2317 AN: 4806

European-Finnish (FIN) AF: 0.364 AC: 3843 AN: 10558

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 31992 AN: 67960

Other (OTH) AF: 0.519 AC: 1094 AN: 2108

Alfa AF: 0.296 Hom.: 629

Bravo AF: 0.523

Asia WGS AF: 0.591 AC: 2054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.27
DANN	Benign	0.69
PhyloP100		-1.7
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: rs6564903; hg19: chr16-81653657;