rs191552868

chr19-44703407-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001039213.4(CEACAM16):c.96C>T(p.Ser32=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,613,780 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (6 hom.)
• Consequence: CEACAM16 NM_001039213.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.223

Genes affected

CEACAM16 (HGNC:31948): (CEA cell adhesion molecule 16, tectorial membrane component) The protein encoded by this gene is a secreted glycoprotein that in mouse interacts with tectorial membrane proteins in the inner ear. The encoded adhesion protein is found in cochlear outer hair cells and appears to be important for proper hearing over an extended frequency range. Defects in this gene likely are a cause of non-syndromic autosomal dominant hearing loss. [provided by RefSeq, May 2012]

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 19-44703407-C-T is Benign according to our data. Variant chr19-44703407-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 226512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-44703407-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.223 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00183 (279/152306) while in subpopulation AMR AF= 0.00961 (147/15296). AF 95% confidence interval is 0.00834. There are 2 homozygotes in gnomad4. There are 133 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEACAM16	NM_001039213.4	c.96C>T	p.Ser32=	synonymous_variant	3/7	ENST00000587331.7
CEACAM16	XM_017026795.2	c.96C>T	p.Ser32=	synonymous_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEACAM16	ENST00000587331.7	c.96C>T	p.Ser32=	synonymous_variant	3/7	1	NM_001039213.4	P1
CEACAM16-AS1	ENST00000662585.1	n.382-4230G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00184 AC: 280 AN: 152188 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00975

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00144

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00198 AC: 491 AN: 248354 Hom.: 4 AF XY: 0.00168 AC XY: 227 AN XY: 134844

Gnomad AFR exome AF: 0.000195

Gnomad AMR exome AF: 0.00788

Gnomad ASJ exome AF: 0.000299

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.000836

Gnomad NFE exome AF: 0.00165

Gnomad OTH exome AF: 0.00133

GnomAD4 exome AF: 0.00160 AC: 2332 AN: 1461474 Hom.: 6 Cov.: 32 AF XY: 0.00154 AC XY: 1117 AN XY: 727048

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.00901

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000921

Gnomad4 NFE exome AF: 0.00158

Gnomad4 OTH exome AF: 0.00179

GnomAD4 genome AF: 0.00183 AC: 279 AN: 152306 Hom.: 2 Cov.: 32 AF XY: 0.00179 AC XY: 133 AN XY: 74470

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.00961

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000942

Gnomad4 NFE AF: 0.00144

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00136 Hom.: 0

Bravo AF: 0.00266

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00120

EpiControl AF: 0.00172

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 30, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2023	CEACAM16: BP4, BP7, BS2 -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 24, 2014

Ser32Ser in exon 3 of CEACAM16: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 1.7% (6/362) of mi xed American chromosomes from a broad population by the 1000 Genomes Project (ht tp://www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs191552868). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	2.7
Dann	Benign	0.59

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: rs191552868; hg19: chr19-45206677;